crossing96/oncoscreening huggingface dataset:
Curcumin as Treatment for Bladder Cancer: A Preclinical Study of Cyclodextrin-Curcumin Complex and BCG as Intravesical Treatment in an Orthotopic Bladder Cancer Rat Model.	OBJECTIVE: To evaluate the antitumor effect of cyclodextrin-curcumin complex (CDC) on human and rat urothelial carcinoma cells in vitro and to evaluate the effect of intravesical instillations of CDC, BCG, and the combination in vivo in the AY-F344 orthotopic bladder cancer rat model. Curcumin has anticarcinogenic activity on urothelial carcinoma and is therefore under investigation for the treatment of non-muscle invasive bladder cancer. Curcumin and BCG share immunomodulating pathways against urothelial carcinoma. METHODS: Curcumin was complexed with cyclodextrin to improve solubility. Four human urothelial carcinoma cell lines and the AY-27 rat cell line were exposed to various concentrations of CDC in vitro. For the in vivo experiment, the AY-27 orthotopic bladder cancer F344 rat model was used. Rats were treated with consecutive intravesical instillations of CDC, BCG, the combination of CDC+BCG, or NaCl as control. RESULTS: CDC showed a dose-dependent antiproliferative effect on all human urothelial carcinoma cell lines tested and the rat AY-27 urothelial carcinoma cell line. Moreover, intravesical treatment with CDC and CDC+BCG results in a lower percentage of tumors (60% and 68%, respectively) compared to BCG (75%) or control (85%). This difference with placebo was not statistically significant (p=0.078 and 0.199, respectively). However, tumors present in the placebo and BCG-treated rats were generally of higher stage. CONCLUSIONS: Cyclodextrin-curcumin complex showed an antiproliferative effect on human and rat urothelial carcinoma cell lines in vitro. In the aggressive orthotopic bladder cancer rat model, we observed a promising effect of CDC treatment and CDC in combination with BCG.	bladder
Lumbrokinase/paclitaxel nanoparticle complex: potential therapeutic applications in bladder cancer.	BACKGROUND: Lumbrokinase (LK) is an enzyme complex with antithrombotic, antioxidant, antitumor, and immunomodulatory effects. It has been extensively studied and used in clinical anti-tumor therapy. However, its half-life is short, its bioavailability is low, and its toxicity and side effects are great, which greatly limit its clinical application. Therefore, LK is often combined with other drugs (such as immune agents, hormones, or Chinese herbal medicine) to reduce its dosage and side effects and to improve its anti-tumor effects. METHODS AND RESULTS: Here, we described an LK/paclitaxel (PTX) nanocarrier based on poly(ethylene glycol)-b-(poly(ethylenediamine l-glutamate)-g-poly(ε-benzyoxycarbonyl-l-lysine)-r-poly(l-lysine)) (PEG-b-(PELG-g-(PZLL-r-PLL))). In the present study, LK and PTX were loaded by electrostatic and/or hydrophobic effects under mild conditions, thereby increasing the half-life and bioavailability of the drugs via the sustained release and enhancement of tumor site enrichment by the LK/PTX/PEG-b-(PELG-g-(PZLL-r-PLL)) complex through passive targeting. In this study, using bladder cancer cells (J82 cells) and rat bladder cancer model as the object, the structure of the nanocarrier, the relationship between drugs composition and antitumor properties were systematically studied. CONCLUSION: We propose that the block copolymer PEG-b-(PELG-g-(PZLL-r-PLL)) may function as a potent nanocarrier for augmenting anti-bladder cancer pharmacotherapy, with unprecedented clinical benefits.	bladder
Chaperone-assisted selective autophagy in healthy and papillomavirus-associated neoplastic urothelium of cattle.	Chaperone-assisted selective autophagy (CASA) is a newly-described selective tension-induced macroautophagy pathway mediated by Bag3 that is believed to be essential for mechanotransduction in skeletal muscle and to be an important regulator of the immune system. We investigated CASA machinery both in healthy and in fifteen papillomavirus-associated neoplastic bovine urothelium. The components of CASA complex, that comprises the molecular chaperones HspA8/Hsc70 and Hsp8B/Hsp22 and the cochaperones Bag3 and STUB1/CHIP, were studied by molecular, microscopic and submicroscopic investigations. CASA complex was found to be constitutively expressed in healthy bovine urothelium; its expression increased in urothelial cancers of cattle, namely thirteen papillary carcinomas and two papillary urothelial neoplasm of low malignant potential (PUNLMPs). We suggest that basal levels of CASA are important in the healthy urothelium which interfaces with the community of urinary microbiota thus representing an important epithelial cell-autonomous mechanism of antibacterial defense. Co-immunoprecipitation studies using an antibody against bovine papillomavirus E5 protein revealed that the oncoprotein co-localized with CASA complex in urothelial cancer cells. This suggests that infection by BPV E5 could influence cell behaviour by interfering with basal autophagy processes although this study did not conclusively show that this interaction increased the expression of CASA proteins. In neoplastic urothelium, CASA could be involved in regulating fundamental cellular processes such adhesion, migration, and proliferation and so might influence the biological behaviour of urothelial tumors in cattle.	bladder
Patient-reported outcomes of blue-light flexible cystoscopy with hexaminolevulinate in the surveillance of bladder cancer: results from a prospective multicentre study.	OBJECTIVE: To evaluate blue-light flexible cystoscopy (BLFC) with hexaminolevulinate in the office surveillance of patients with non-muscle-invasive bladder cancer with a high risk of recurrence by assessing its impact on pain, anxiety, subjective value of the test and patient willingness to pay. MATERIALS AND METHODS: A prospective, multicentre, phase III study was conducted during which the Patient-Reported Outcomes Measurement Information System (PROMIS) Anxiety, Pain and 'Was It Worth It' questionnaires were administered at baseline, after surveillance with BLFC and after resection for those referred to the operating room. Comparisons of scores were performed between groups. RESULTS: A total of 304 patients were enrolled, of whom 103 were referred for surgical examination. Of these, 63 were found to have histologically confirmed malignancy. Pain levels were low throughout the study. Anxiety levels decreased after BLFC (∆ = -2.6), with a greater decrease among those with negative pathology results (P = 0.051). No differences in anxiety were noted based on gender, BLFC results, or test performance (true-positive/false-positive). Most patients found BLFC 'worthwhile' (94%), would 'do it again' (94%) and 'would recommend it to others' (91%), with no differences based on BLFC results or test performance. Most patients undergoing BLFC (76%) were willing to pay out of pocket. CONCLUSIONS: Anxiety decreased after BLFC in patients with negative pathology, including patients with false-positive results. Most of the patients undergoing BLFC were willing to pay out of pocket, found the procedure worthwhile and would recommend it to others, irrespective of whether they had a positive BLFC result or whether this was false-positive after surgery.	bladder
Update on the Treatment of Metastatic Urothelial Carcinoma.	Platinum-based combination chemotherapy has been the standard of care in the first-line treatment of metastatic urothelial carcinoma (mUC). Treatment of metastatic disease following progression on platinum-based regimens has evolved significantly in the last few years. Clinical trials are currently ongoing to determine how best to use and sequence these treatments. In this minireview, we will review current first-line treatment options in both cisplatin fit and cisplatin unfit patients and advances in first- and second-line treatments including chemotherapy and immunotherapy. This review reports key findings from the clinical trials especially highlighting the importance of PD-1 and PD-L1 inhibitors in the treatment of bladder/urothelial carcinomas.	bladder
Pre-diagnostic circulating insulin-like growth factor-I and bladder cancer risk in the European Prospective Investigation into Cancer and Nutrition.	Previous in vitro and case-control studies have found an association between the insulin-like growth factor (IGF)-axis and bladder cancer risk. Circulating concentrations of IGF-I have also been found to be associated with an increased risk of several cancer types; however, the relationship between pre-diagnostic circulating IGF-I concentrations and bladder cancer has never been studied prospectively. We investigated the association of pre-diagnostic plasma concentrations of IGF-I with risk of overall bladder cancer and urothelial cell carcinoma (UCC) in a case-control study nested within the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort. A total of 843 men and women diagnosed with bladder cancer between 1992 and 2005 were matched with 843 controls by recruitment centre, sex, age at recruitment, date of blood collection, duration of follow-up, time of day and fasting status at blood collection using an incidence density sampling protocol. Odds ratios (ORs) and 95% confidence intervals (CIs) were calculated using conditional logistic regression with adjustment for smoking status. No association was found between pre-diagnostic circulating IGF-I concentration and overall bladder cancer risk (adjusted OR for highest versus lowest fourth: 0.91, 95% CI: 0.66-1.24, p(trend) = 0.40) or UCC (n of cases = 776; 0.91, 0.65-1.26, p(trend) = 0.40). There was no significant evidence of heterogeneity in the association of IGF-I with bladder cancer risk by tumour aggressiveness, sex, smoking status, or by time between blood collection and diagnosis (p(heterogeneity) > 0.05 for all). This first prospective study indicates no evidence of an association between plasma IGF-I concentrations and bladder cancer risk.	bladder
Clinical evaluation of two consecutive UroVysion fluorescence in situ hybridization tests to detect intravesical recurrence of bladder cancer: a prospective blinded comparative study in Japan.	BACKGROUND: We evaluated the use of UroVysion fluorescence in situ hybridization tests to detect the intravesical recurrence of bladder cancer during follow-up after a transurethral resection of bladder tumor (TURBT). METHODS: In this prospective, blinded, comparative study, 486 patients treated by TURBT within the prior 2 years were registered at 12 centers. Urine cytology and UroVysion tests were performed once or twice at a central testing laboratory. For the patients with no suspicious findings of bladder cancer in the first analysis, the same examination set was repeated 3 months later as the second analysis. Totals of 468 and 399 patients were eligible for the first and second analyses, respectively. We determined the sensitivity and specificity of two consecutive UroVysion tests. RESULTS: Bladder cancers were identified in 44 patients at the first analysis. The UroVysion test had 50.0% (95% CI 35.2-64.8%) sensitivity and 72.4% (68.3-76.8%). Urine cytology had 4.5% (0.0-10.7%) sensitivity and 99.8% (99.3-100.0%) specificity. The concordant rate of the first and second UroVysion test results was 72% (kappa coefficient 0.157). Interestingly, the patients with two consecutive positive UroVysion test results had the highest cancer detection rate (14.8%), which is greater than those of the patients with a positive result in either (7.2%) or neither (1.2%) of the two tests at the 3-month follow-up. CONCLUSIONS: The UroVysion test provided higher sensitivity than urine cytology to detect bladder cancer during post-TURBT follow-up. Two consecutive UroVysion tests might be a better indicator to predict intravesical recurrence.	bladder
Immunotherapy with cancer peptides in combination with intravesical bacillus Calmette-Guerin for patients with non-muscle invasive bladder cancer.	PURPOSE: A phase I study using two peptide vaccines derived from M phase phosphoprotein 1 (MPHOSPH1) and DEP domain containing 1 (DEPDC1) demonstrated promising results for the treatment of advanced bladder cancer. Therefore, we further tested the ability of these peptides to prevent recurrence after transurethral resection of the bladder tumor in patients with non-muscle invasive bladder cancer (NMIBC). MATERIALS AND METHODS: 127 patients were enrolled in a multicenter, non-randomized phase II clinical trial. The primary endpoint was recurrence-free survival (RFS) rate, and secondary endpoints were safety and immunological response. HLA-A24-restricted peptides were subcutaneously administered in addition to intravesical BCG therapy. The exploratory endpoint evaluated differences of RFS rate between HLA-A*2402-positive (A24(+)) and -negative (A24(-)) groups. RESULTS: A 2-year RFS rate in all patients was 74.0%. The RFS rate in the A24(+) group (n = 75) and in the A24(-) group (n = 52) were 76.0 and 71.2%, respectively. This vaccine therapy was well-tolerated and feasible. MPHOSPH1 and DEPDC1 peptide-specific cytotoxic T lymphocyte responses were observed in 75.8 and 77.5% of the A24(+) group, respectively. Patients having both peptide-specific CTL responses showed significantly better RFS than patients without CTL response (P = 0.014). In the A24(+) group, patients who had positive reaction at the injection sites (RAI) had significantly lower rates of recurrence than RAI-negative patients (P = 0.0019). CONCLUSIONS: Cancer peptide vaccines in combination with intravesical BCG therapy demonstrated good immunogenicity and safety, and may provide benefit for preventing recurrence of NMIBC.	bladder
Management of ureteric duplications identified during robotic cystectomy and intracorporeal urinary diversion.	Ureteral duplication is rarely seen malformation that could be diagnosed during radiological imaging. Herein, we present 5 patients with ureteral duplication who underwent robotic radical cystectomy with intracorporeal urinary diversion for bladder cancer. Preoperative computerized tomography did not show presence of a ureteral duplication in any patient and all were identified intraoperatively. A Wallace type uretero-ureteral anastomosis was performed in all patients. During the follow-up period, we did not detect any ureterointestinal anastomotic strictures or complication related to the presence of a ureteral duplication following robotic cystectomy. We conclude that ureteral duplication might be missed during preoperative radiological imaging, might be a surprising and challenging issue for the robotic surgeon that could be safely managed intraoperatively.	bladder
Long-term outcomes of high-grade T1 bladder cancer treated with intravesical bacillus Calmette-Guérin: experience of a single center.	BACKGROUND: To assess the outcomes of patients with high-grade (HG) pT1 bladder cancer (BC) treated with intravesical BCG therapy. METHODS: The study population consisted of 185 patients with HG pT1 BC treated between 1998 and 2010. We aimed to determine recurrence-free (RFS) and progression-free survival (PFS), as well as the predictors of RFS and PFS. RESULTS: Overall, 143 (77.3%) patients were males. Median age was 72 years (IQR: 66-78). Tumor size was ≥3 cm in 100 (54.1%) individuals. Most patients had single tumors (125; 67.6%). Primary, progressive and recurrent patterns of presentation were observed in 146 (78.9%), 21 (11.4%), and 18 (9.7%) cases, respectively. After 2nd-look TURB, 127 (68.6%) patients had no residual disease, 44 (23.8%) had Ta/CIS, and 14 (7.6%) had T1 HG BC. Twenty-two (11.9%) patients experience early recurrence after BCG. Of these, 12 patients (54.5%) were diagnosed with Ta/CIS, while 10 (45.5%) were diagnosed with HG pT1 BC. The median follow-up was 93 months (IQR: 63-147). Ten-year RFS and PFS rates were 69.6 and 79.2%. In multivariable Cox regression models, female gender (HR=2.41; P=0.001), progressive (HR=2.03; P=0.030) and recurrent (HR=3.87; P<0.001) pattern of presentation emerged as independent predictors of RFS, while age ≥70 years (HR=2.13; P=0.027), presence of multiple tumors (HR=2.06; P=0.019), and early recurrence (HR=3.88; P<0.001) emerged as independent predictors of PFS. CONCLUSIONS: Intravesical BCG appears to be an effective treatment for HG pT1 BC. Caution should be used in patients aged ≥70 years, with multiple tumors or experiencing early recurrence.	bladder
KIRs gene content diversity in Iranians with urothelial bladder cancer.	Natural killer cells (NK) are the first arm of the innate immune system in defense against tumor and infection. 16 distinct Killer-cell immunoglobulin-like receptors (KIRs) are involved in orchestrating NK cell function. The KIR family contains 14 genes and 2 pseudogenes. Six of these receptors are activating (aKIR) and the remaining receptors are inhibitory KIRs (iKIR), that interact with MHC-I molecules; producing signals which stop NK cell function. In the current study, we have investigated the genomic diversity of KIRs and determining the A and B haplotypes as well as Bx subsets in 119 patients with bladder cancer and 200 healthy controls to find out if there is an association between KIR system and susceptibility to bladder cancer. Polymerase chain reaction with sequence specific primers (SSP-PCR) typing system was used to determine the KIR gene profile. The results implicated decreased frequency of inhibitory KIR2DL2 and activating KIR2DS2 while increased frequency of CxT4 genotypes in patients compared with healthy controls. Among Bx subsets, the CxT4 gene cluster is more frequent in bladder cancer patients compared to controls. Our results provide a conclusion that KIR2S2 and KIR2L2 may play a protective role against bladder cancer development while the CxT4 gene cluster may underlie susceptibility to bladder cancer in Iranian population.	bladder
Effects of multi and selective targeted tyrosine kinase inhibitors on function and signaling of different bladder cancer cells.	BACKGROUND: Signaling of receptor tyrosine kinases (RTK) is dysregulated in various malignancies including bladder cancer. RTKs trigger pro-proliferative, anti-apoptotic and metastatic signaling pathways. Here, we assessed the effects of a selective tyrosine kinase inhibitor (TKI) (BGJ398) targeting fibroblast growth factor receptor (FGFR) and a pan-TKI (TKI258) targeting (FGFR), platelet derived growth factor receptor (PDGFR) and vascular endothelial growth factor receptor (VEGFR) in bladder cancer cells. METHODS: Levels of mRNA transcripts were measured in nine human cell lines by quantitative RT-PCR. Cell function was assessed for viability, colony formation, migration, apoptosis and proliferation. Protein mediators of signal transduction were measured by Western-blot. RESULTS: mRNA transcripts encoding RTK-related components, transcription factors, epithelial and mesenchymal transition (EMT) markers as well as cell cycle and apoptotic factors were determined in the cell lines. Principal component analysis ordered one epithelial-like cell cluster (5637, BFTC-905, MGHU4, RT112) and one mesenchymal-like cell cluster (T24, UMUC3, HU456, TCC-SUP). Cell response scores towards TKI258 and BGJ398 treatment were heterogeneous between cell lines and correlated with certain transcript levels. Analysis of signal transduction pathways revealed inhibition of fibroblast growth factor receptor (FGFR) signaling and induction of cell cycle dependent kinase (CDKN1A, p21) in epithelial-like cells differing in this regard from responses to mesenchymal-like cells that exhibited inhibition of mitogen-activated protein kinase (MAPK). CONCLUSION: RTK and EMT related transcript analysis separate bladder cancer cells in two clusters. Functional responses towards TKI258 and BGJ398 treatment of bladder Fcancer cells were heterogeneous with deviating effects on signaling and possibly different therapeutic outcome.	bladder
Urothelial bladder cancer may suppress perforin expression in CD8+ T cells by an ICAM-1/TGFβ2 mediated pathway.	The immune system plays a significant role in urothelial bladder cancer (UBC) progression, with CD8+ T cells being capable to directly kill tumor cells using perforin and granzymes. However, tumors avoid immune recognition by escape mechanisms. In this study, we aim to demonstrate tumor immune escape mechanisms that suppress CD8+ T cells cytotoxicity. 42 patients diagnosed with UBC were recruited. CD8+ T cells from peripheral blood (PB), sentinel nodes (SN), and tumor were analyzed in steady state and in vitro-stimulated conditions by flow cytometry, RT-qPCR, and ELISA. Mass spectrometry (MS) was used for identification of proteins from UBC cell line culture supernatants. Perforin was surprisingly found to be low in CD8+ T cells from SN, marked by 1.8-fold decrease of PRF1 expression, with maintained expression of granzyme B. The majority of perforin-deficient CD8+ T cells are effector memory T (TEM) cells with exhausted Tc2 cell phenotype, judged by the presence of PD-1 and GATA-3. Consequently, perforin-deficient CD8+ T cells from SN are low in T-bet expression. Supernatant from muscle invasive UBC induces perforin deficiency, a mechanism identified by MS where ICAM-1 and TGFβ2 signaling were causatively validated to decrease perforin expression in vitro. Thus, we demonstrate a novel tumor escape suppressing perforin expression in CD8+ T cells mediated by ICAM-1 and TGFβ2, which can be targeted in combination for cancer immunotherapy.	bladder
High expression of enhancer RNA MARC1 or its activation by DHT is associated with the malignant behavior in bladder cancer.	Enhancer RNAs (eRNAs), a subclass of noncoding RNA from enhancers, have biological functions in gene expression. However, their potential role in bladder cancer (BCa) remains largely unknown. The present study investigated the functional role of androgen-associated androgen receptor (AR) mediated-eRNA MARC1 (eMARC1) in BCa progression. Cell proliferation, migration, and apoptosis of BCa cell lines (5637 and T24) with different eMARC1 expression levels or treated with 5α-dehydrotestosterone (DHT) were investigated. In the current study, we discovered that eMARC1 was highly expressed in BCa tissues and cell lines, and eMARC1 overexpression promoted the progression of BCa cells, while knockdown of eMARC1 suppressed tumorigenesis. DHT treatment significantly elevated eMARC1 expression levels, which also facilitated cell proliferation, motility, and inhibited cell apoptosis. We further found that eMARC1 silencing impaired the androgenic effect of DHT in BCa cells. These results suggested that eMARC1 exerted its effects on BCa cell progression, and DHT promoted bladder cancer progression by activating eMARC1.	bladder